While chemotherapy has helped to improve survival for cancer patients, the side effects lead to substantial detrimental effects on quality of life tht can be debilitating; these side effects, including cognitive impairments, have become a major focus of research. Chemotherapy-related cognitive impairment (CRCI) is characterized by difficulty in memory, attention, concentration and executive function. CRCI is most pronounced and severe during chemotherapy (in up to 80% of patients), however, it can last for years following treatment in up to 35% of survivors. With over 13 million cancer survivors in the US, it is estimated that up to 4 million survivors could be living with long-lasting effects of CRCI. CRCI is particularly significant because long-term cognitive impairment can develop, CRCI negatively impacts quality of life, and CRCI can affect treatment adherence. I'm currently conducting a NCI K Award in patient-oriented research investigating interventions targeting inflammation to alleviate cognitive difficulties in breast cancer patients receiving chemotherapy; my laboratory focuses solely on CRCI research. One of the main hypotheses in our field is that inflammation may drive cognitive impairment in these patients. While this is becoming well-accepted in our field, there is a gap in understanding the nature of this inflammatory response as most clinical research studies have limited access to biological correlates of CRCI. There is also a lack of investigators that can carefully assess neuro-immune factors in basic science models as well as in people. I am proposing to use my knowledge in basic immunology, neuroimmunology, and neuroscience with my behavioral research training in cognitive science, neuropsychology and clinical cancer control to address these gaps in the field. While this research focuses on CRCI, it has broad implications for many areas of cancer control and survivorship. Part I of this application involves careful assessment and understanding of the role of inflammation on brain function and neuroinflammation in chemotherapy animal models (using a breast cancer chemotherapy paradigm; Part IA) and following up with analyzing possible etiological factors in a breast cancer patient cohort that is being treated with the same chemotherapy regimen (Part IB). In Part II of this application, we will utilize animal models to develop and test intervention for cancer-related cognitive impairment (this is not commonly done in cancer control research) which will allow us to move forward with the most successful interventions for testing in clinical research. Overall, this proposal will allow us to better understand immunologic and neurotoxic effects of CRCI, develop interventions for CRCI, and improve the overall public health burden of this troublesome side effect.